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The identification of fungal-specific pathogenic mechanisms is considered a crucial step to current antifungal drug development and represents a significant goal to increase the efficacy and reduce host toxicity. Although the overall architecture of F1FO-ATP synthase is largely conserved in both fungi and mammals, the subunit i\/j (Su i\/j, Atp18) and subunit k (Su k, Atp19) are proteins not found in mammals and specific to fungi. Here, the role of Su i\/j and Su k in Candida albicans was characterized by an in vivo assessment of the virulence and in vitro growth and mitochondrial function. Strikingly, the atp18\u0394\/\u0394 mutant showed significantly reduced pathogenicity in systemic murine model. However, this substantial defect in infectivity exists without associated defects in mitochondrial oxidative phosphorylation or proliferation in vitro. Analysis of virulence-related traits reveals normal in both mutants, but shows cell wall defects in composition and architecture in the case of atp18\u0394\/\u0394. We also find that the atp18\u0394\/\u0394 mutant is more susceptible to attack by macrophages than wild type, which may correlate well with the abnormal cell wall function and increased sensitivity to oxidative stress. In contrast, no significant changes were observed in any of these studies for the atp19\u0394\/\u0394. These results demonstrate that the fungal-specific Su i\/j, but not Su k of F1FO-ATP synthase may play a critical role in C. albicans infectivity and represent another opportunity for new therapeutic target investigation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Lay Abstract<\/jats:title>\n                  <jats:p>This study aims to investigate biological functions of fungal-specific subunit i\/j and subunit k of ATP synthase in C. albicans oxidative phosphorylation and virulence potential. Our results revealed that subunit i\/j, and not subunit k, is critical for C. albicans pathogenicity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mmy\/myaa094","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T12:09:23Z","timestamp":1604405363000},"page":"639-652","source":"Crossref","is-referenced-by-count":6,"title":["The fungal-specific subunit i\/j of F1FO-ATP synthase stimulates the pathogenicity of <i>Candida albicans<\/i> independent of oxidative phosphorylation"],"prefix":"10.1093","volume":"59","author":[{"given":"Yajing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China"},{"name":"Institute of Mycology, Jinan University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First 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Guangdong, China"},{"name":"Institute of Mycology, Jinan University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, District of Columbia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China"},{"name":"Institute of Mycology, Jinan University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"2021070523533583900_bib1","doi-asserted-by":"crossref","first-page":"4566","DOI":"10.1038\/s41467-019-12381-5","article-title":"Fungal dissemination is limited by liver macrophage 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